It has only recently been known that different collagens exist within different tissues of the vertebrates and that these collagens are differentially modified by specific enzymatic reactions, but essentially nothing is known concerning the mechanisms which are involved in determining the type of collagen which a given, terminally- differentiated cell will synthesize, or the role that post-translational modifications have in the orderly processes of tissue differentiation. It is proposed to study the regulation of the qualitative synthesis of collagen in pure populations of chick vertebral chondrocytes which have induced to "dedifferentiate" by the addition to the medium of embryo extract of 5-bromo-2'deoxyuridine, since it has been shown that this dedifferentiation is accompanied by a switch in the type of collagen which is synthesized. The studies on the mechanisms of the switch will focus on biochemical changes which occur during the cell cycle since experiments by the applicant have shown that in order to elicit the switch, cells must be capable of replication and the effect appears to be localized to a specific portion of the cell cycle. For these studies synchronized populations of cells will be employed. The applicant proposes to characterize the newly-synthesized collagens from various differentiating tissues in cell or organ culture. Labelled, purified alpha chains will be examined for type and content of lysine, hydroxylysine and hydroxylysine glycosides. It is expected that meaningful temporal patterns will emerge which may suggest that these embryonic collagens and their modified derivatives serve important "instructional" roles in development. It is hoped that answers as to the controls over the synthesis of collagen type and subsequent modifications will give hints as to the biochemical changes which occur in the embryo and underwrite the process of cellular differentiation. Such knowledge would be valuable to studies of pathological alterations and birth defects involving connective tissue.